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Predictors of Fatal and Non-Fatal Overdose Following Prescription of Opioids for Chronic Pain: A Systematic Review and Meta-Analysis of Observational Studies
40 Pages Posted: 3 Mar 2023
More...Abstract
Background: Factors associated with opioid overdose when prescribed for chronic pain are unclear. We aimed to explore predictors of opioid overdose after prescription for chronic pain.
Methods: We searched MEDLINE, EMBASE, CINAHL, PsycINFO and Web of Science up to October 30, 2022, for observational studies that explored predictors of opioid overdose following prescription for chronic pain. Paired reviewers independently extracted data, assessed risk of bias and certainty of evidence. We performed random-effects meta-analyses for all factors reported by ≥2 studies.
Findings: Twenty-eight studies (23,963,716 patients) reported the association of 103 factors with opioid overdose after prescription for chronic pain. Moderate- to high-certainty evidence supported large associations with opioid overdose and a history of overdose (OR 5·85 [95% CI 3·78 to 9·04]), higher opioid dose (OR 2·57 [95% CI 2·08 to 3·18] for every 90-mg increment in daily morphine equivalent dose), ≥3 prescribers (OR 4·68 [95% CI 3·57 to 6·12]), ≥4 dispensing pharmacies (OR 4·92 [95% CI 4·35 to 5·57]), fentanyl (OR 2·80 [95% CI 2·30 to 3·41]), long-acting opioid formulations (OR 1·92 [95% CI 1·51 to 2·45]), current substance use disorder (OR 2·62 [95% CI 2·09 to 3·27]), any mental health diagnosis (OR 2·12 [95% CI 1·73 to 2·61]), depression (OR 2·22 [95% CI 1·57 to 3·14]), bipolar disorder (OR 2·07 [95% CI 1·77 to 2·41]), or pancreatitis (OR 2·00 [95% CI 1·52 to 2·64]). These factors were associated with absolute risks ranging from 2‰ to 6‰ for fatal and 4‰ to 12‰ for non-fatal overdose.
Interpretation: Minimizing high-dose opioid prescribing, fentanyl, long-acting formulations, multiple opioid prescribers or pharmacies, and opioid prescribing to chronic pain patients that have previously overdosed or present with a current substance use disorder, depression, bipolar disorder, or other mental illness, or pancreatitis may reduce the risk of opioid overdose when prescribed for chronic pain.
Funding: This study was supported by a grant from Health Canada. JWB is supported, in part, by a Canadian Institutes of Health Research Canada Research Chair in the prevention and management of chronic pain.
Declaration of Interest: All authors have completed the ICMJE uniform disclosure form and declare: no financial support from any industry for the submitted work.
Keywords: Opioids, Chronic Pain, Overdose, Death, Predictor, Meta-Analysis
Suggested Citation: Suggested Citation